Abstract
Spermidine has therapeutic effects in many diseases including as heart diastolic function, myopathic defects and neurodegenerative disorders via autophagy activation. Autophagy has been found to mitigate cell apoptosis in intervertebral disc degeneration (IDD). Accordingly, we theorize that spermidine may have beneficial effects on IDD via autophagy stimulation. In this study, spermidine's effect on IDD was evaluated in tert‐butyl hydroperoxide (TBHP)‐treated nucleus pulposus cells of SD rats in vitro as well as in a puncture‐induced rat IDD model. We found that autophagy was actuated by spermidine in nucleus pulposus cells. In addition, spermidine treatment weakened the apoptotic effects of TBHP in nucleus pulposus cells. Spermidine increased the expression of anabolic proteins including Collagen‐II and aggrecan and decreased the expression of catabolic proteins including MMP13 and Adamts‐5. Additionally, autophagy blockade using 3‐MA reversed the beneficial impact of spermidine against nucleus pulposus cell apoptosis. Autophagy was thus important for spermidine's therapeutic effect on IDD. Spermidine‐treated rats had an accentuated T2‐weighted signal and a diminished histological degenerative grade than vehicle‐treated rats, showing that spermidine inhibited intervertebral disc degeneration in vivo. Thus, spermidine protects nucleus pulposus cells against apoptosis through autophagy activation and improves disc, which may be beneficial for the treatment of IDD.
Highlights
Lower back pain (LBP) is a muscular complaint that can cause societal and economic problems in some instances due to intervertebralZengming Zheng and Zhouguang Wang contribute to this work.disc degeneration (IDD).[1]
Our research demonstrated that spermidine administration significantly increases nucleus pulposus (NP) cell autophagy and blocks apoptosis with low inherent toxicity
Our study demonstrated that spermidine treatment induces autophagy in NP cells, which blocked NP cell apoptosis and degenerate protein expression induced by oxidative stress
Summary
Lower back pain (LBP) is a muscular complaint that can cause societal and economic problems in some instances due to intervertebral. Disc degeneration (IDD).[1] Intervertebral disc degeneration (IDD) is intertwined with the process of ageing and occurs at a high incidence It is one of the primary causes of neck pain, lower back pain and eventual disability, which significantly affects the quality of life and working ability of patients.[2] Because the world’s population is living longer, IDD is a large burden on public health and subsequent. Spermidine application to cell culture media or in vivo application to animals has been found to prolong lifespan in various model organisms similar to autophagy induction.[14,15] Oral supplementation of spermidine is capable of extending the lifespan of mice and exerts cardioprotective effects by reducing cardiac hypertrophy and preserving diastolic function in aged mice These effects are mediated in part by control of autophagic flux.[16] Recently, it was demonstrated that spermidine could stimulate autophagy in various tissues including the brain,[17] eye[18] and heart.[19] We theorize that spermidine might exert protective effects on IDD through autophagy stimulation.
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